Distinguishing adrenal cortical carcinomas and adenomas: a study of clinicopathological features and biomarkers

Histopathology. 2014 Mar;64(4):567-76. doi: 10.1111/his.12283. Epub 2013 Nov 23.

Abstract

Aims: To determine clinicopathological criteria and molecular markers helpful in distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs).

Methods and results: We analysed retrospectively the clinical and pathological features of 50 adrenal cortical tumours, and tested the expression of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4 by immunohistochemistry. We found that tumour size, tumour weight, hormonal function and the Weiss system are all high-efficacy criteria for differentiating malignant from benign tumours (P < 0.001). MiR483-3p was overexpressed in 68% (17 of 25) of ACCs compared to 12% (three of 25) of ACAs (P < 0.05). Using a combination of miR483-3p and Smad4 improved diagnostic accuracy. Molecular markers were then tested in an independent set of 15 borderline tumours. We confirmed that the combined use of miR483-3p and Smad4 immunochemistry can complement the Weiss score in the diagnosis of ACC in cases that display borderline histology.

Conclusions: Tumour size, tumour weight, hormonal function and the Weiss system are useful clinicopathological criteria that can result in accurate diagnosis of most ACCs and ACAs. In challenging cases, miR483-3p and Smad4 expression may help in distinguishing these two entities.

Keywords: adrenal cortical tumours; clinicopathological features; diagnosis; differentiation; hsa-mir-483-3p; in-situ hybridization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / diagnosis*
  • Adrenal Cortex Neoplasms / genetics
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenocortical Adenoma / diagnosis*
  • Adrenocortical Adenoma / genetics
  • Adrenocortical Adenoma / metabolism*
  • Adrenocortical Carcinoma / diagnosis*
  • Adrenocortical Carcinoma / genetics
  • Adrenocortical Carcinoma / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism*
  • Retrospective Studies
  • Smad4 Protein / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • IGF2 protein, human
  • MIRN483 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • SMAD4 protein, human
  • Smad4 Protein
  • Insulin-Like Growth Factor II